Dysfunctions of cellular context-sensitivity in neurodevelopmental learning disabilities.

Pyramidal neurons have a pivotal role in the cognitive capabilities of neocortex. Though they have been predominantly modeled as integrate-and-fire point processors, many of them have another point of input integration in their apical dendrites that is central to mechanisms endowing them with the sensitivity to context that underlies basic cognitive capabilities. Here we review evidence implicating impairments of those mechanisms in three major neurodevelopmental disabilities, fragile X, Down syndrome, and fetal alcohol spectrum disorders. Multiple dysfunctions of the mechanisms by which pyramidal cells are sensitive to context are found to be implicated in all three syndromes. Further deciphering of these cellular mechanisms would lead to the understanding of and therapies for learning disabilities beyond any that are currently available.

Effects of a 12-week telehealth exercise intervention on gait speed and gait deviations in adults with Down syndrome.

BACKGROUND: Altered gait patterns and reduced walking speed are commonly reported in adults with Down syndrome (DS). Research on the effects of DS-specific exercise programmes on adults with DS is lacking. The purpose of this quasi-experimental study was to evaluate the changes in gait deviations and walking speed in adults with DS after a DS-specific exercise programme. METHODS: Twenty participants underwent a 12-week, DS-specific exercise programme in a telehealth format. Before and after the intervention, gait deviations were assessed with the Ranchos Los Amigos Observational Gait Analysis form, and comfortable walking speed was evaluated with the 4-m walk test. RESULTS: We observed increased comfortable walking speed and reduced gait deviations in the whole gait cycle in adults with DS after the intervention. There were fewer gait deviations during single-leg stance and swing-limb advancement and at the hip, knee and ankle joints after the 12-week exercise programme. CONCLUSIONS: Gait speed and observable gait impairments in adults with DS significantly improved following a 12-week telehealth exercise programme.

Sleep disordered breathing improvement prevents worsening of autonomic dysfunction in children with Down syndrome.

BACKGROUND: Resolution of sleep disordered breathing (SDB) in typically developing children normalises heart rate variability (HRV), a measure of autonomic control, to that of non-snoring controls. Children with Down Syndrome (DS) have dampened heart rate variability (HRV) but the effect of treatment is not known. To assess the effect of improvement of SDB on autonomic control we compared HRV in children with DS whose SDB improved over 2 y, to those whose SDB did not improve. METHODS: 24 children (3-19 y) had a baseline and follow-up polysomnographic study 2 y later. Improved SDB was defined as a reduction in obstructive apnea hypopnea index (OAHI) to ≤ 50% of baseline. Children were grouped into Improved (n = 12) and Unimproved (n = 12). Power spectral analysis of the ECG determined low frequency (LF), high frequency (HF) power and the LF/HF ratio. Seven children in the Improved and 2 in the Unimproved group were treated following the baseline study. RESULTS: In the Unimproved group at follow-up, LF power was lower compared to baseline during N3 and Total Sleep (p < 0.05 for both). HF power was lower during REM (p < 0.05). HRV remained unchanged between studies in the Improved group. CONCLUSION: Autonomic control worsened as indicated by lower LF and HF power in children whose SDB was not improved. In contrast, in those children with improved SDB, autonomic control remained the same, suggesting improvement in SDB severity prevents further worsening of autonomic control in children with DS.

Autoimmunity in Down's syndrome via cytokines, CD4 T cells and CD11c+ B cells.

Down's syndrome (DS) presents with a constellation of cardiac, neurocognitive and growth impairments. Individuals with DS are also prone to severe infections and autoimmunity including thyroiditis, type 1 diabetes, coeliac disease and alopecia areata1,2. Here, to investigate the mechanisms underlying autoimmune susceptibility, we mapped the soluble and cellular immune landscape of individuals with DS. We found a persistent elevation of up to 22 cytokines at steady state (at levels often exceeding those in patients with acute infection) and detected basal cellular activation: chronic IL-6 signalling in CD4 T cells and a high proportion of plasmablasts and CD11c+TbethighCD21low B cells (Tbet is also known as TBX21). This subset is known to be autoimmune-prone and displayed even greater autoreactive features in DS including receptors with fewer non-reference nucleotides and higher IGHV4-34 utilization. In vitro, incubation of naive B cells in the plasma of individuals with DS or with IL-6-activated T cells resulted in increased plasmablast differentiation compared with control plasma or unstimulated T cells, respectively. Finally, we detected 365 auto-antibodies in the plasma of individuals with DS, which targeted the gastrointestinal tract, the pancreas, the thyroid, the central nervous system, and the immune system itself. Together, these data point to an autoimmunity-prone state in DS, in which a steady-state cytokinopathy, hyperactivated CD4 T cells and ongoing B cell activation all contribute to a breach in immune tolerance. Our findings also open therapeutic paths, as we demonstrate that T cell activation is resolved not only with broad immunosuppressants such as Jak inhibitors, but also with the more tailored approach of IL-6 inhibition.

A reassessment of Jackson's checklist and identification of two Down syndrome sub-phenotypes.

Down syndrome (DS) is characterised by several clinical features including intellectual disability (ID) and craniofacial dysmorphisms. In 1976, Jackson and coll. identified a checklist of signs for clinical diagnosis of DS; the utility of these checklists in improving the accuracy of clinical diagnosis has been recently reaffirmed, but they have rarely been revised. The purpose of this work is to reassess the characteristic phenotypic signs and their frequencies in 233 DS subjects, following Jackson's checklist. 63.77% of the subjects showed more than 12 signs while none showed less than 5, confirming the effectiveness of Jackson's checklist for the clinical diagnosis of DS. An association between three phenotypic signs emerged, allowing us to distinguish two sub-phenotypes: Brachycephaly, short and broad Hands, short Neck (BHN), which is more frequent, and "non-BHN". The strong association of these signs might be interpreted in the context of the growth defects observed in DS children suggesting decreased cell proliferation. Lastly, cognitive assessments were investigated for 114 subjects. The lack of association between the presence of a physical sign or the number of signs present in a subject and cognitive skills disproves the stereotype that physical characteristics are predictive of degree of ID.

Visual and Refractive Status of Children With Down's Syndrome and Nystagmus.

Purpose: Children with Down's syndrome (DS) are known to have poorer visual acuity than neurotypical children. One report has shown that children with DS and nystagmus also have poor acuity when compared to typical children with nystagmus. What has not been established is the extent of any acuity deficit due to nystagmus and whether nystagmus affects refractive error within a population with DS. Methods: Clinical records from the Cardiff University Down's Syndrome Vision Research Unit were examined retrospectively. Binocular visual acuity and refraction data were available for 50 children who had DS and nystagmus and 176 children who had DS but no nystagmus. Data were compared between the two groups and with published data for neurotypical children with nystagmus. Results: The study confirms the deficit in acuity in DS, compared to neurotypical children, of approximately 0.2 logMAR and shows a deficit attributable to nystagmus of a further 0.2 logMAR beyond the first year of life. Children with both DS and nystagmus clearly have a significant additional impairment. Children with DS have a wide range of refractive errors, but nystagmus increases the likelihood of myopia. Prevalence and axis direction of astigmatism, on the other hand, appear unaffected by nystagmus. Conclusions: Nystagmus confers an additional visual impairment on children with DS and must be recognized as such by families and educators. Children with both DS and nystagmus clearly need targeted support.

Reactive Species in Progeroid Syndromes and Aging-Related Processes.

Significance: Reactive species have been classically considered causative of age-related degenerative processes, but the scenario appears considerably more complex and to some extent counterintuitive than originally anticipated. The impact of reactive species in precocious aging syndromes is revealing new clues to understand and perhaps challenge the resulting degenerative processes. Recent Advances: Our understanding of reactive species has considerably evolved, including their hormetic effect (beneficial at a certain level, harmful beyond this level), the occurrence of diverse hormetic peaks in different cell types and organisms, and the extended type of reactive species that are relevant in biological processes. Our understanding of the impact of reactive species has also expanded from the dichotomic damaging/signaling role to modulation of gene expression. Critical Issues: These new concepts are affecting the study of aging and diseases where aging is greatly accelerated. We discuss how notions arising from the study of the underlying mechanisms of a progeroid disease, Cockayne syndrome, represent a paradigm shift that may shed a new light in understanding the role of reactive species in age-related degenerative processes. Future Issues: Future investigations urge to explore established and emerging notions to elucidate the multiple contributions of reactive species in degenerative processes linked to pathophysiological aging and their possible amelioration. Antioxid. Redox Signal. 37, 208-228.

Relationship between trunk muscle strength, reaching ability and balance in children with Down syndrome - A cross-sectional study.

BACKGROUND: Children with Down Syndrome (DS) present with neuromuscular disturbances leading to delayed developmental milestones, poor quality of movement and poor balance. The aim of this study is to discuss the role of trunk muscle strength in the functional performance of children with DS. METHODOLOGY: 28 children were recruited in the study, 14 with DS and 14 age and gender-matched controls. Trunk muscle strength, reaching ability and balance were assessed using a Handheld Dynamometer, Modified Functional Reach test and Pediatric Balance Scale, respectively. RESULTS: Children with DS present with poorer trunk muscle strength, reaching ability and balance as compared to typically developing (TD) children. There was a positive correlation between trunk muscle strength and lateral reaching in children with DS. A strong to moderate correlation was observed between the trunk muscle strength and balance in children with DS. DISCUSSION: Children with DS demonstrated a significantly weak trunk muscle groups. Lateral reaching distance is reduced due to the poor proximal control and they present with near-normal forward reach distance attributed to compensation using the lower trunk muscles. They exhibit poor balance in the components that require a small base of support. CONCLUSION: Children with DS exhibit weak trunk muscles along with lesser reaching distance and poor balance. Also, trunk muscle strength influences lateral reaching ability. Trunk muscle strength, mainly trunk extensors impacted functional balance in sitting, standing and while performing transfers.

Skeletal Deficits in Male and Female down Syndrome Model Mice Arise Independent of Normalized Dyrk1a Expression in Osteoblasts.

Trisomy 21 (Ts21) causes alterations in skeletal development resulting in decreased bone mass, shortened stature and weaker bones in individuals with Down syndrome (DS). There is a sexual dimorphism in bone mineral density (BMD) deficits associated with DS with males displaying earlier deficits than females. The relationships between causative trisomic genes, cellular mechanisms, and influence of sex in DS skeletal abnormalities remain unknown. One hypothesis is that the low bone turnover phenotype observed in DS results from attenuated osteoblast function, contributing to impaired trabecular architecture, altered cortical geometry, and decreased mineralization. DYRK1A, found in three copies in humans with DS, Ts65Dn, and Dp1Tyb DS model mice, has been implicated in the development of postnatal skeletal phenotypes associated with DS. Reduced copy number of Dyrk1a to euploid levels from conception in an otherwise trisomic Ts65Dn mice resulted in a rescue of appendicular bone deficits, suggesting DYRK1A contributes to skeletal development and homeostasis. We hypothesized that reduction of Dyrk1a copy number in trisomic osteoblasts would improve cellular function and resultant skeletal structural anomalies in trisomic mice. Female mice with a floxed Dyrk1a gene (Ts65Dn,Dyrk1afl/wt) were mated with male Osx-Cre+ (expressed in osteoblasts beginning around E13.5) mice, resulting in reduced Dyrk1a copy number in mature osteoblasts in Ts65Dn,Dyrk1a+/+/Osx-Cre P42 male and female trisomic and euploid mice, compared with littermate controls. Male and female Ts65Dn,Dyrk1a+/+/+ (3 copies of DYRK1A in osteoblasts) and Ts65Dn,Dyrk1a+/+/Osx-Cre (2 copies of Dyrk1a in osteoblasts) displayed similar defects in both trabecular architecture and cortical geometry, with no improvements with reduced Dyrk1a in osteoblasts. This suggests that trisomic DYRK1A does not affect osteoblast function in a cell-autonomous manner at or before P42. Although male Dp1Tyb and Ts65Dn mice exhibit similar skeletal deficits at P42 in both trabecular and cortical bone compartments between euploid and trisomic mice, female Ts65Dn mice exhibit significant cortical and trabecular deficits at P42, in contrast to an absence of genotype effect in female Dp1Tyb mice in trabecular bone. Taken together, these data suggest skeletal deficits in DS mouse models and are sex and age dependent, and influenced by strain effects, but are not solely caused by the overexpression of Dyrk1a in osteoblasts. Identifying molecular and cellular mechanisms, disrupted by gene dosage imbalance, that are involved in the development of skeletal phenotypes associated with DS could help to design therapies to rescue skeletal deficiencies seen in DS.

Neuronal excitatory-to-inhibitory balance is altered in cerebral organoid models of genetic neurological diseases.

The neuro-physiological properties of individuals with genetic pre-disposition to neurological disorders are largely unknown. Here we aimed to explore these properties using cerebral organoids (COs) derived from fibroblasts of individuals with confirmed genetic mutations including PRNPE200K, trisomy 21 (T21), and LRRK2G2019S, which are associated with Creutzfeldt Jakob disease, Down Syndrome, and Parkinson's disease. We utilized no known disease/healthy COs (HC) as normal function controls. At 3-4 and 6-10 months post-differentiation, COs with mutations showed no evidence of disease-related pathology. Electrophysiology assessment showed that all COs exhibited mature neuronal firing at 6-10 months old. At this age, we observed significant changes in the electrophysiology of the COs with disease-associated mutations (dCOs) as compared with the HC, including reduced neuronal network communication, slowing neuronal oscillations, and increased coupling of delta and theta phases to the amplitudes of gamma oscillations. Such changes were linked with the detection of hypersynchronous events like spike-and-wave discharges. These dysfunctions were associated with altered production and release of neurotransmitters, compromised activity of excitatory ionotropic receptors including receptors of kainate, AMPA, and NMDA, and changed levels and function of excitatory glutamatergic synapses and inhibitory GABAergic synapses. Neuronal properties that modulate GABAergic inhibition including the activity of Na-K-Cl cotransport 1 (NKCC1) in Cl- homeostasis and the levels of synaptic and extra-synaptic localization of GABA receptors (GABARs) were altered in the T21 COs only. The neurosteroid allopregnanolone, a positive modulator of GABARs, was downregulated in all the dCOs. Treatment with this neurosteroid significantly improved the neuronal communication in the dCOs, possibly through improving the GABAergic inhibition. Overall, without the manifestation of any disease-related pathology, the genetic mutations PRNPE200K, T21, and LRRK2G2019S significantly altered the neuronal network communication in dCOs by disrupting the excitatory-to-inhibitory balance.

Context Fear Conditioning in Down Syndrome Mouse Models: Effects of Trisomic Gene Content, Age, Sex and Genetic Background.

Down syndrome (DS), trisomy of the long arm of human chromosome 21 (Hsa21), is the most common genetic cause of intellectual disability (ID). Currently, there are no effective pharmacotherapies. The success of clinical trials to improve cognition depends in part on the design of preclinical evaluations in mouse models. To broaden understanding of the common limitations of experiments in learning and memory, we report performance in context fear conditioning (CFC) in three mouse models of DS, the Dp(16)1Yey, Dp(17)1Yey and Dp(10)1Yey (abbreviated Dp16, Dp17 and Dp10), separately trisomic for the human Hsa21 orthologs mapping to mouse chromosomes 16, 17 and 10, respectively. We examined female and male mice of the three lines on the standard C57BL/6J background at 3 months of age and Dp17 and Dp10 at 18 months of age. We also examined female and male mice of Dp17 and Dp10 at 3 months of age as F1 hybrids obtained from a cross with the DBA/2J background. Results indicate that genotype, sex, age and genetic background affect CFC performance. These data support the need to use both female and male mice, trisomy of sets of all Hsa21 orthologs, and additional ages and genetic backgrounds to improve the reliability of preclinical evaluations of drugs for ID in DS.

Estimación de la masa grasa por medio de indicadores antropométricos en jóvenes con síndrome de Down / Estimation of fat mass by anthropometric indicators in young people with Down syndrome

Introducción: la evaluación de la composición corporal es relevante y útil para diseñar intervenciones de estilos de vida saludables y estrategias nutricionales.Objetivos: verificar las relaciones existentes entre los indicadores de adiposidad y la masa grasa (MG), y validar ecuaciones que permitan predecir la MG en jóvenes con síndrome de Down (SD).Métodos: se efectuó un estudio transversal en 48 jóvenes con SD (24 hombres y 24 mujeres). Se evaluaron el peso, la estatura, la circunferencia de la cintura (CC) y la circunferencia de la cadera (CCa). Se calcularon el índice de masa corporal (IMC), el índice de adiposidad corporal (IAC), el índice cintura-cadera (ICC) y el índice cintura-estatura (ICE). Se evaluó la MG mediante absorciometría de rayos X de doble energía (DXA). Resultados: la edad de los hombres era de 19,3 ± 3,0 años y la de las mujeres de 18,9 ± 1,9 años; el peso era de 73,6 ± 14,3 kg en los hombres y de 75,8 ± 20,3 kg en las mujeres; finalmente, la estatura de los hombres era de 168,9 ± 6,5 cm y la de las mujeres de 156,3 ± 6,2 cm. En los hombres, las correlaciones entre la MG (DXA) y los parámetros IMC, CC, CCa, ICE, IAC e ICE oscilaron entre r = 0,01 y r = 0,89; en las mujeres, entre r = 0,10 y r = 0,97. Las correlaciones más altas se observaron con el IMC y la CC en ambos sexos (hombres, r = 0,78 a 0,92 y mujeres, r = 0,83 a 0,97). Se generaron ecuaciones de regresión para estimar la MG en los hombres (R2 = 84 %) y en las mujeres (R2 = 96 %). Se calcularon los percentiles de MG según la DXA y con cada ecuación. Conclusiones:hubo correlaciones positivas significativas del IMC y la CC con la MG. Estos indicadores fueron determinantes para desarrollar ecuaciones que estiman la MG de los jóvenes con SD. Los resultados sugieren su uso y aplicación para evaluar, clasificar y monitorizar los niveles de adiposidad corporal en contextos clínicos y epidemiológicos. (AU)

Introduction: the assessment of body composition is relevant and useful for designing interventions for healthy lifestyles and nutritional strategies. Objective: our goal was to verify the relationships between adiposity indicators with fat mass (FM), and to validate equations that allow predicting FM in young people with Down syndrome (SD). Methods: a cross-sectional study was carried out in 48 young people with DS (24 men and 24 women). Weight, height, waist circumference (WC), and hip circumference (HC) were evaluated. Body mass index (BMI), body adiposity index (BAI), waist-to-hip index (WHI), and waist-to-height index (WHtR) were calculated. FM was evaluated by dual energy X-ray absorptiometry (DXA). Results: age in men was 19.3 ± 3.0 years, and in women it was 18.9 ± 1.9 years; weight was 73.6 ± 14.3 kg in men and 75.8 ± 20.3 kg in women, and height in men was 168.9 ± 6.5 cm, and in women it was 156.3 ± 6.2 cm. In males the correlations between FM (DXA) with BMI, WC, HC, WHtR, BAI and WHtR ranged from r = 0.01 to r = 0.89, and in females from r = 0.10 to r = 0.97. The highest correlations were observed with BMI and WC in both sexes (males r = 0.78 to 0.92, and females r = 0.83 to 0.97). Regression equations were generated to estimate FM in males (R2 = 84 %) and in females (R2 = 96 %). Percentiles were calculated for MG per DXA and for each equation. Conclusions: there were significant positive correlations between BMI and WC with FM. These indicators were decisive for developing equations that estimate FM in young people with DS. The results suggest its potential use and application to evaluate, classify and monitor body fat levels in clinical and epidemiological contexts. (AU)

Tabla para niños con síndrome de Down talla/edad de 0 a 3 años

Obstructive sleep apneas naturally occur in mice during REM sleep and are highly prevalent in a mouse model of Down syndrome.

STUDY OBJECTIVES: The use of mouse models in sleep apnea study is limited by the belief that central (CSA) but not obstructive sleep apneas (OSA) occur in rodents. We aimed to develop a protocol to investigate the presence of OSAs in wild-type mice and, then, to apply it to a validated model of Down syndrome (Ts65Dn), a human pathology characterized by a high incidence of OSAs. METHODS: In a pilot study, nine C57BL/6J wild-type mice were implanted with electrodes for electroencephalography (EEG), neck electromyography (nEMG), and diaphragmatic activity (DIA), and then placed in a whole-body-plethysmographic (WBP) chamber for 8 h during the rest (light) phase to simultaneously record sleep and breathing activity. CSA and OSA were discriminated on the basis of WBP and DIA signals recorded simultaneously. The same protocol was then applied to 12 Ts65Dn mice and 14 euploid controls. RESULTS: OSAs represented about half of the apneic events recorded during rapid-eye-movement-sleep (REMS) in each experimental group, while the majority of CSAs were found during non-rapid eye movement sleep. Compared with euploid controls, Ts65Dn mice had a similar total occurrence rate of apneic events during sleep, but a significantly higher occurrence rate of OSAs during REMS, and a significantly lower occurrence rate of CSAs during NREMS. CONCLUSIONS: Mice physiologically exhibit both CSAs and OSAs. The latter appear almost exclusively during REMS, and are highly prevalent in Ts65Dn. Mice may, thus, represent a useful model to accelerate the understanding of the pathophysiology and genetics of sleep-disordered breathing and to help the development of new therapies.

Comprehensive phenotypic analysis of the Dp1Tyb mouse strain reveals a broad range of Down syndrome-related phenotypes.

Down syndrome (DS), trisomy 21, results in many complex phenotypes including cognitive deficits, heart defects and craniofacial alterations. Phenotypes arise from an extra copy of human chromosome 21 (Hsa21) genes. However, these dosage-sensitive causative genes remain unknown. Animal models enable identification of genes and pathological mechanisms. The Dp1Tyb mouse model of DS has an extra copy of 63% of Hsa21-orthologous mouse genes. In order to establish whether this model recapitulates DS phenotypes, we comprehensively phenotyped Dp1Tyb mice using 28 tests of different physiological systems and found that 468 out of 1800 parameters were significantly altered. We show that Dp1Tyb mice have wide-ranging DS-like phenotypes, including aberrant erythropoiesis and megakaryopoiesis, reduced bone density, craniofacial changes, altered cardiac function, a pre-diabetic state, and deficits in memory, locomotion, hearing and sleep. Thus, Dp1Tyb mice are an excellent model for investigating complex DS phenotype-genotype relationships for this common disorder.

Forebrain Shh overexpression improves cognitive function and locomotor hyperactivity in an aneuploid mouse model of Down syndrome and its euploid littermates.

Down syndrome (DS) is the leading genetic cause of intellectual disability and causes early-onset dementia and cerebellar hypoplasia. The prevalence of attention deficit hyperactivity disorder is elevated in children with DS. The aneuploid DS mouse model "Ts65Dn" shows prominent brain phenotypes, including learning and memory deficits, cerebellar hypoplasia, and locomotor hyperactivity. Previous studies indicate that impaired Sonic hedgehog (Shh) signaling contributes to neurological phenotypes associated with DS and neurodegenerative diseases. However, because of a lack of working inducible Shh knock-in mice, brain region-specific Shh overexpression and its effects on cognitive function have not been studied in vivo. Here, with Gli1-LacZ reporter mice, we demonstrated that Ts65Dn had reduced levels of Gli1, a sensitive readout of Shh signaling, in both hippocampus and cerebellum at postnatal day 6. Through site-specific transgenesis, we generated an inducible human Shh knock-in mouse, TRE-bi-hShh-Zsgreen1 (TRE-hShh), simultaneously expressing dually-lipidated Shh-Np and Zsgreen1 marker in the presence of transactivator (tTA). Double transgenic mice "Camk2a-tTA;TRE-hShh" and "Pcp2-tTA;TRE-hShh" induced Shh overexpression and activated Shh signaling in a forebrain and cerebellum, respectively, specific manner from the perinatal period. Camk2a-tTA;TRE-hShh normalized locomotor hyperactivity and improved learning and memory in 3-month-old Ts65Dn, mitigated early-onset severe cognitive impairment in 7-month-old Ts65Dn, and enhanced spatial cognition in euploid mice. Camk2a-tTA;TRE-hShh cohort maintained until 600days old showed that chronic overexpression of Shh in forebrain from the perinatal period had no effect on longevity of euploid or Ts65Dn. Pcp2-tTA;TRE-hShh did not affect cognition but mitigated the phenotype of cerebellar hypoplasia in Ts65Dn. Our study provides the first in vivo evidence that Shh overexpression from the perinatal period protects DS brain integrity and enhances learning and memory in normal mice, indicating the broad therapeutic potential of Shh ligand for other neurological conditions. Moreover, the first inducible hShh site-specific knock-in mouse could be widely used for spatiotemporal Shh signaling regulation.

One-year effects of bifocal and unifocal glasses on executive functions in children with Down syndrome in a randomized controlled trial.

Appropriate glasses can improve visual functioning of children with Down syndrome (DS), but it is unknown if such interventions influence their cognitive impairments. In a randomized controlled trial with 1-year follow-up. Children with DS (2-16 years) were provided either bifocal glasses (add +2.5 Dioptres; n = 50) or unifocal glasses (n = 52). Executive functions were assessed pre- and post-intervention with the task-based Minnesota Executive Function Scale (MEFS) and with questionnaires, BRIEF-P and BRIEF, parents' and teachers' version. Intervention effects and associations between executive functions, (near) vision and ocular alignment were analysed. Intervention improved MEFS-Total-scores in the bifocal group (p = 0.002; Cohen's d = 0.60) but not in the unifocal group (p = 0.191; Cohen's d = 0.24). Post-intervention, there was no intergroup difference (p = 0.120; Cohen's d = 0.34). Post-intervention, higher MEFS-scores were associated with better visual acuities (crowded near p = 0.025; uncrowded near p = 0.019; distant p = 0.045). Pre-post changes in MEFS-scores correlated significantly with improved ocular alignment (p = 0.040). Exploratory analysis of the questionnaires showed improved teacher-rated BRIEF-scores in both groups (bifocals: p = 0.014, Cohen's d = 1.91; unifocals: p = 0.022, Cohen's d = 1.46), with no intergroup difference (p = 0.594; Cohen's d = 0.23). These results demonstrate positive effects of wearing better-correcting glasses on executive functioning in children with DS, suggesting a link between their visual and executive functioning. However, the relative contributions of distant and near vision need further study.

Delivering a new diagnosis of Down syndrome: Parent experience.

Down syndrome is one of the most common chromosomal abnormalities. In 2014, in conjunction with the passing of House Bill 552, the Ohio Department of Health released a Down syndrome fact sheet to be given to parents at time of diagnosis to answer basic questions regarding the diagnosis. Our survey helps us to understand parental experience in receiving a new Down syndrome diagnosis including information provided. An electronic survey was created and distributed to members of established Down syndrome parent groups in Ohio. Questions assessed the parental experience at the time of receiving a Down syndrome. We also looked at parent perceptions after the implementation of a Down syndrome fact sheet. Responses were collected regarding experience at the time of diagnosis and broadly categorized into a trichotomy of positive experience (>5), neutral experience (=5), and negative experience (<5). Parents report an overall negative experience when receiving a new diagnosis of Down syndrome (mean of 4 on scale of 0-10), which did not increase after 2014 (p >0.05). Eighty-five percent of parents with children born in 2014 or after report that they did not receive the Ohio Department of Health Down syndrome fact sheet. Legislation regarding a diagnosis of Down syndrome exists in 20 states with significant variability, readability of those fact sheets. Legislation requiring accurate information be given to families was not always followed, and printed literature alone did not correlate with improved parent experience; additional efforts are necessary to ensure that the experience receiving a diagnosis of Down syndrome is not a negative one.